title: PTPRO promoter methylation is predictive of poorer outcome for HER2-positive breast cancer: indication for personalized therapy.
abstract: BACKGROUND
  Protein Tyrosine Phosphatase Receptor-type O (PTPRO) has recently been in the spotlight as a tumor suppressor, whose encoding gene is frequently methylated in cancers. We examined the methylation status of the PTPRO gene promoter in breast cancer and evaluated the correlation between PTPRO promoter methylation and both clinicopathological parameters and prognosis of breast cancer patients.
  
  
  METHODS
  Two hundred twenty-one formalin-fixed, paraffin-embedded (FFPE) tumor tissues, 20 FFPE normal adjacent tissues and 24 matched plasma samples, collected from primary breast cancer patients, were assessed for PTPRO gene promoter methylation using methylation-specific PCR. Associations of promoter methylation with clinicopathological parameters were evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect on survival.
  
  
  RESULTS
  175 samples gave identifiable PCR products, of which 130 cases (74.3%) had PTPRO gene promoter methylation. PTPRO methylation correlated with higher histological grade (P = 0.028), but not other clinical parameters. Multivariate analysis indicated that overall survival (OS) was significantly poorer in HER2-positive, but not ER-positive patients with methylated-PTPRO. Methylated-PTPRO was detectable in matched plasma samples and only observed in plasma from patients whose corresponding primary tumors were also methylated.
  
  
  CONCLUSIONS
  PTPRO methylation is a common event in the primary breast cancer and can be reliably detected in peripheral blood samples. PTPRO methylation is associated with poor survival only in HER2-positive patients, suggesting use of PTPRO methylation as a prognostic factor for breast cancer and for optimizing individualized therapy for HER2-positive patients.
authors.affiliation: Department of Integrative Oncology, Affiliated Cancer Hospital of Shantou University Medical College, Shantou 515041, China. haozhang@stu.edu.cn.
authors.forename: Yi-Teng
authors.initials: YT
authors.lastname: Huang
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Li
authors.forename: Chen
authors.initials: C
authors.lastname: Ke
authors.forename: Zhou
authors.initials: Z
authors.lastname: Li
authors.forename: Zong-Tai
authors.initials: ZT
authors.lastname: Li
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Zou
authors.forename: Xiao-Xuan
authors.initials: XX
authors.lastname: Zheng
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Chen
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D001943:Breast Neoplasms / Q000145:classification / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D016612:Paraffin Embedding; D057285:Precision Medicine; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000235:genetics*; D016707:Tissue Fixation; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; C508053:ERBB2 protein, human; C516888:PTPRO protein, human